Marlena Dudek-Makuch, Pharm. D., Development Expert, Curtis Health Caps
The basic function of vitamin D is to control bone metabolism as well as calcium and phosphorus homeostasis, which is closely related to the mineralization of the bone system. However, in recent years, considerable research has been carried out, both in vitro and in vivo, which has helped to detect non-calcemic actions of vitamin D metabolites and confirm the so-called pleiotropic, i.e., multidirectional action of vitamin D [1]. SARS-CoV-2, responsible for the COVID-19 pandemics, has brought about an explosion of interest both in the mechanisms of infection, as well as in potential risk factors of the disease. Vitamin D has become a factor that may be involved in both these areas.  


Retrospective research comparing the levels of vitamin D in COVID-19 patients and healthy individuals Retrospective research held between 1 March and 14 April 2020 evaluated data of 107 patients from Switzerland. The patients developed symptoms of acute respiratory infection, fever or no fever, muscle ache or sudden loss of smell and taste. In order to confirm infection with SARS-CoV-2, a nasopharyngeal swab was taken and subjected to PCR analysis. The patients had the levels of vitamin D3 metabolite (25-hydroxycholecalciferol; 25(OH)D3) in blood measured. An additional control group was made up of patients who had had their levels of 25(OH)D3 measured in an analogous period (1 March to 14 April) of 2019. Conclusions:
  • A correlation has been shown between vitamin D level and the risk of developing COVID-19; patients with a positive SARS-CoV-2 test result (2020 PCR Pos group) had significantly statistically lower levels of 25(OH)D3 — 11.1 ng/ml compared to negative patients (2020 PCR Neg group) – 24.6 ng/ml and to healthy individuals in 2019 (2019 group) – 24.6 ng/ml.
  • No significant difference has been observed between the 2020 negative PCR group and the 2019 group (Fig. 1) [2].
Fig. 1. Concentration of 25(OH)D3 in groups under evaluation [2].   Statistical evaluation of the correlation between the mean vitamin D level and the COVID-19 mortality and the number of COVID-19 cases
  • A correlation has been shown between the population level of vitamin D in the European society and the number of COVID-19 patients and the COVID-19 mortality (Fig. 2) [3].
Fig. 2. Correlation between the vitamin D level and the mortality and the number of cases in the population [3].


An appropriate level of vitamin D may, on the one hand, strengthen the body’s immunity and reduce the risk of developing the disease, while on the other, as a factor modulating the immune response, may alleviate COVID-19 symptoms and prevent “cytokine storm” and acute respiratory distress syndrome (ARDS).

Vitamin D as immune response controller

Once the pathogen has entered the body, immune cells, such as macrophages, produce 1,25(OH)2D which binds with the VDR receptor and may control innate immune response, both by inducing and hindering various trails (Fig. 3A) [4].   Fig. 3A Vitamin D impact on immune response and inflammation.             Fig. 3B COVID-19 pathophysiology and development of ARDS. ACE-2 – angiotensin converting enzyme 2; ARDS – acute respiratory distress syndrome; IL – interleukin; NFκB – transcription factor; NO – nitrogen oxide; SARS-CoV-2, severe acute respiratory syndrome 2; Th1, Th2, Th17 – Th lymphocyte types; TLR – toll-like receptor; TNFα – tumour necrosis factor alpha; VDR, vitamin D receptor [4].   It has been shown that:
  • Vitamin D is responsible for stimulating the production of cathelicidin peptides and active defensins against bacteria, enveloped and non-enveloped viruses and fungi [4, 5],
  • Vitamin D deficiency hinders the macrophages’ ability to mature, to produce specific surface antigens, to produce acid phosphatase lysosomal enzyme and to secrete H2O2, which is inherently related to the body’s defence mechanism against pathogens [6],
  • Vitamin D is responsible for the expression of Toll-like receptors (TLR), which are supposed to recognize pathogens and stimulate the release of cytokines and reactive oxygen forms [4].

SARS-CoV-2 infection and cytokine storm

SARS-CoV-2 infects lung epithelial cells through the receptor of angiotensin-converting enzyme 2 (ACE-2), causing macrophages, neutrophils and T-lymphocytes to activate and thus raise the level of pro-inflammatory cytokines (IL-1, IL-6, TNF-α). In some cases, the immune system is overactive resulting in overproduction of cytokines and the so-called “cytokine storm”, which causes vast destruction of the lung tissue and results in some patients developing active respiratory distress syndrome (ARDS) which poses a high risk of death (Fig. 3B). Vitamin D is capable of modulating the expression of various genes, and thus capable of controlling the immune response:
  • It modulates macrophage response, preventing the release of too many inflammatory cytokines and chemokines (IL-1, IL-6, IL-12, TNF alpha and IL-17) and promoting the production of anti-inflammatory cytokines (IL-10) [4, 5],
  • It directly hinders the nuclear factor NFκB, reducing thus the expression of pro-inflammatory cytokines [4],
  • It suppresses the proliferation of T-lymphocytes and the resulting transfer of Th1 lymphocytes to Th2 lymphocytes, which results in a lower level of pro-inflammatory cytokines [4].
  The aforementioned research shows that an appropriate level of vitamin D boosts immunity, furthermore, through the modulation of immune response, vitamin D may alleviate COVID-19 symptoms and prevent ARDS. There is no scientific consensus at present as to the optimum dose of vitamin D supplement in the case of COVID-19. It is, however, assumed that the optimum concentration of 1,25(OH)2D3 in blood is at least 40–50 ng/ml; in order to counteract the effects of vitamin D deficiency a dose of 2000–5000 IU per day is recommended [7]. Since excess and overdose of vitamin D are rare, some experts recommend that specific patients, in particular adults in high-risk groups (people 70 years of age or older, people suffering from diabetes, coronary and vascular diseases, obesity), consider taking 10000 UI/day from time to time, in order to quickly compensate for vitamin D deficiency. [5].


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Marlena Dudek-Makuch, Pharm. PhD Development Expert at Curtis Health Caps, Wysogotowo
20 years of experience in phytochemical and biological research, as well as scientific information (assistant professor at the Chair and Institute of Pharmacognosy of the Medical University in Poznań). Author of experimental works and works supported with research examples in the field of isolation and identification of plant-based compounds and evaluation of their biological activity. Lecturer at “Herbs in practice and therapy” post-graduate studies since 2015. Currently employed at CHC in the R&D Section, Regulatory Department. Responsible, in particular, for drawing up Expert reports (clinical and non-clinical) for medicinal products, clinical report for Rx switch to OTC drugs, clinical evaluation for medicinal products and activity in the field of supervision over the safety of medicinal products, as well as for evaluating the safety of plant-based materials used in medicinal products, medical devices and dietary supplements.

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